Kelso A, Gough N M
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital Victoria, Australia.
Growth Factors. 1989;1(2):165-77. doi: 10.3109/08977198909029126.
Two pathways for the activation of lymphokine synthesis in murine T cell clones and polyclonal T cell blast populations were identified. One was induced by ligands of the T cell receptor (TCR) and led to high production of GM-CSF, IFN-gamma, and IL-3. The other was induced by IL-2 and led to production of lower levels of GM-CSF and IFN-gamma with relatively little IL-3 synthesis. Cyclosporin A (CsA) markedly inhibited TCR-independent production of lymphokine mRNA and protein at concentrations where IL-2-dependent stimulation of lymphokine production and proliferation was unaffected. Stimulation of lymphokine synthesis by phorbol myristate acetate (PMA) and the Ca2+ ionophore ionomycin, or by ionomycin alone, mimicked the TCR-dependent response. PMA on its own was a preferential stimulus for GM-CSF production, but, whereas CsA did not inhibit PMA stimulation of polyclonal T cell blasts, T cell clones displayed a biphasic response in which CsA only inhibited stimulation by high PMA concentrations. The data suggest that Ca2(+)-independent (CsA-resistant) T cell activation induces synthesis of GM-CSF and IFN-gamma but is a poor stimulus for IL-3 production. On the other hand, when Ca2(+)-dependent (CsA-sensitive) pathways are activated by TCR binding or by a Ca2+ ionophore, production of high levels of all three lymphokines can be induced.
在小鼠T细胞克隆和多克隆T细胞母细胞群体中，鉴定出了两条激活淋巴因子合成的途径。一条途径由T细胞受体（TCR）的配体诱导，导致GM-CSF、IFN-γ和IL-3的高产量。另一条途径由IL-2诱导，导致GM-CSF和IFN-γ的产量较低，而IL-3合成相对较少。环孢素A（CsA）在不影响IL-2依赖性淋巴因子产生和增殖刺激的浓度下，显著抑制了不依赖TCR的淋巴因子mRNA和蛋白质的产生。佛波酯肉豆蔻酸酯（PMA）和Ca2+离子载体离子霉素或单独的离子霉素刺激淋巴因子合成，模拟了依赖TCR的反应。单独的PMA是GM-CSF产生的优先刺激物，但是，虽然CsA不抑制PMA对多克隆T细胞母细胞的刺激，但T细胞克隆表现出双相反应，其中CsA仅抑制高浓度PMA的刺激。数据表明，不依赖Ca2+（抗CsA）的T细胞激活诱导GM-CSF和IFN-γ的合成，但对IL-3产生的刺激较弱。另一方面，当依赖Ca2+（对CsA敏感）的途径通过TCR结合或Ca2+离子载体激活时，可以诱导所有三种淋巴因子的高水平产生。
